Macrophages play important roles following injury to the nervous system (40,41). Following axonal injury in the mammalian peripheral nervous system, circulating blood monocytes infiltrate the distal Wallerian degenerating nerve segment (2,5,16,20,40,48). Although Wallerian degeneration of peripheral nerve was initially characterized over 100 years ago (53), the cellular and molecular mechanisms mediating monocyte/macrophage recruitment remain unknown. Cell adhesion molecules (CAMs) on monocytes and endothelial cells have been shown to play critical roles in mediating the transendothelial migration of circulating monocytes into non-neural tissues following various types of injury (4,10,23-25,44,54). A major hypothesis we plan to test is that LFA-1 / ICAM-1, Mac-1 /ICAM-1, and VLA-4 /VCAM-1 monocyte/ endothelial CAM interactions play a critical role in mediating monocyte/macrophage infiltration during Wallerian degeneration of peripheral nerve. Immunocytochemical techniques will be used to determine the expression of the above CAMs on intraneural monocytes/macrophages and endothelial cells during Wallerian degeneration. In addition, several lines of experimental evidence suggest, but by no means prove, that infiltrating macrophages promote axonal regeneration. We plan to determine the role of macrophages in axonal regeneration by preventing or reducing their infiltration following nerve injury by intravenously administering blocking monoclonal antibodies to the above CAMs. Modulation of the macrophage response following injury to the nervous system may lead to new strategies and therapies to minimize damage and promote recovery.